The overall goal of this proposal is to test the efficacy of a novel mechanism to prevent or delay diabetic complications (DC) by enhancing the removal and clearance of toxic glucose metabolites. The objective of this project is to evaluate the effect of over-expression of mouse LZ (mLZ), a non-toxic native peptide, by adenovirus vector based gene transfer in diabetic nude mice in enhancing the removal of AGEs, thus aborting their toxic impact on multiple tissues, herein focusing on the kidney. The specific aims include: Aim 1A. In vivo characterization of mLZ-expressing E1-deleted adenovirus vector (Ad.E1-mLZ), and the determination of the efficacy of hepatoma cells to synthesize and secrete LZ; Aim 1B. Assessment of in vitro anti-AGE activity of mLZ and cellular processing of the mLZ:AGE complex; Aim 2. In vivo testing of optimal gene transfer dosage, secretion and efficacy of mLZ against AGE accumulation and cellular toxicity; and Aim 3. Investigation of the in vivo fate of mLZ:AGE complex and/or potential toxicity in nu/nuSTZ-diabetic mice.